Sialyltransferase STX (ST8SiaII): A novel molecular marker of metastatic neuroblastoma Journal Article


Authors: Cheung, I. Y.; Vickers, A.; Cheung, N. K. V.
Article Title: Sialyltransferase STX (ST8SiaII): A novel molecular marker of metastatic neuroblastoma
Abstract: Polysialic acid (PSA) is highly expressed in many human cancers, including neuroblastoma (NB), and is critical for cellular adhesion, neuronal migration and tumor metastasis. The key enzyme responsible for PSA synthesis is sialyltransferase STX (ST8SiaII). Using quantitative RT-PCR we (i) studied STX expression in 39 NB tumors and 8 cell lines and (ii) examined its potential clinical utility as an early response marker in the bone marrows of the entire cohort of 136 high-risk NB patients treated with an immunotherapy protocol utilizing anti-GD2 antibody 3F8 and GM-CSF. Based on the quantitation of 24 normal marrow and peripheral blood samples, a normalized STX transcript value below the mean + 2SD was defined as negative. Sensitivity of this assay was 1 NB cell in 106 normal mononuclear cells. STX expression was high among NB tumors of all stages, as well as NB cell lines of different phenotypes. Evaluation for early (2.5 months from protocol entry) marrow response by univariate Cox model indicated that STX marker status (positive versus negative) was strongly associated with both progression-free and overall survival (p < 0.0005 for both). Similarly, the STX transcript level of posttreatment marrows was also highly prognostic of outcome (PFS, p = 0.001; OS, p < 0.0005). We conclude that STX mRNA has potential clinical utility as a molecular marker of metastatic NB. © 2006 Wiley-Liss, Inc.
Keywords: child; controlled study; unclassified drug; human cell; major clinical study; disease marker; sensitivity and specificity; reproducibility of results; phenotype; metastasis; bone marrow; proportional hazards models; tumor markers, biological; clinical protocol; cell line, tumor; high risk patient; monoclonal antibody; immunotherapy; mononuclear cell; infant; neuroblastoma; messenger rna; minimal residual disease; neoplasm, residual; reverse transcriptase polymerase chain reaction; rna, messenger; nucleotide sequence; polysialic acid; sialyltransferase; sialyltransferases; predictive value of tests; cell migration; cell adhesion; nerve cell; monoclonal antibody 3f8; granulocyte macrophage colony stimulating factor receptor; marker validation; polysialic acid (psa); sialyltransferase x
Journal Title: International Journal of Cancer
Volume: 119
Issue: 1
ISSN: 0020-7136
Publisher: John Wiley & Sons  
Date Published: 2006-07-01
Start Page: 152
End Page: 156
Language: English
DOI: 10.1002/ijc.21789
PUBMED: 16450393
PROVIDER: scopus
DOI/URL:
Notes: --- - "Cited By (since 1996): 14" - "Export Date: 4 June 2012" - "CODEN: IJCNA" - "Source: Scopus"
Altmetric
Citation Impact
BMJ Impact Analytics
MSK Authors
  1. Nai-Kong Cheung
    648 Cheung
  2. Andrew J Vickers
    880 Vickers
  3. Irene Y Cheung
    96 Cheung